The overall goal of the present project is to elucidate the neuronal mechanisms that underlie decision making. Successful decision making requires consideration of a range of variables including the likelihood of success, the magnitude and quality of the payoff, and the amount of effort required to achieve the outcome. Damage to prefrontal cortex, particularly the orbital and medial regions, produces impairments in decision making. In addition, this region has extensive connections with the basal ganglia, a region implicated in action selection and reinforcement learning. The project will focus on delineating the contribution of the different components of this network to decision making. The first specific aim will examine whether different regions are responsible for processing different variables relating to decisions, or whether a single area is responsible for integrating the information. Our second specific aim will examine the neural mechanisms involved in making comparisons between different choices. For example, how are neural signals modulated when the alternative outcomes are closer in value? Our final specific aim is to examine how positive and negative outcomes to behavioral choices modulate the engagement of frontostriatal regions in decision making. We aim to determine whether there are distinct neuronal populations within the frontal lobe and basal ganglia for responding to positive and negative feedback, as well as identify regions associated with a more generalized learning system that responds to both kinds of feedback. Using multiple methodologies, we will obtain convergent evidence to address each aim. We will measure neuronal signals using a variety of techniques including single-unit neurophysiology and collection of local field potentials (LFPs) in awake, behaving monkeys, functional magnetic resonance imaging (fMRI) in healthy humans, and electrocorticography (ECoG) in epileptic patients undergoing surgerical evaluation. In addition, we will conduct neuropsychological studies in patients with selective frontal and striatal damage to determine the manner in which these neuronal regions contribute to successful decision making in choice behavior. Developmental studies will be conducted, focusing on how children become sensitive to different variables that constrain decision making and setting the stage for subsequent fMRI studies. To strengthen the synergy across these methodologies, we will endeavor to use near-identical behavioral tasks. Basic knowledge about the functional organization of PFC gained from these studies will provide substantial insights into the cognitive and decision making deficits associated with the frontostriatal dysfunction. This includes disorders such as stroke, traumatic brain injury, and degenerative brain diseases such as Parkinson's Disease and frontotemporal dementia.